February 16, 2017

Glycomics Data Club

February 28, 2017
11:30 – 1:00 pm
ROLLINS RESEARCH CENTER 4052 (Biochemistry Conference Room)

O-Glycans in Thrombosis

Renhao Li, PhD
Professor of Pediatrics

Division of Hematology/Oncology

Emory University School of Medicine

Platelets and a plasma protein von Willebrand factor (VWF) play a critical role in the pathogenesis of thrombotic microangiopathy and the associated thrombocytopenia. Our recent study of VWF and its platelet receptor GPIb-IX suggests the involvement of O-linked glycans in regulating the activities of VWF and GPIb-IX, which lead to thrombocytopenia and pro-thrombotic states under certain circumstances. Our studies illustrate the need for new tools of site-specific modifications of O-glycans.


October 21, 2016

Glycomics Data Club

October 25, 2016
12:00 – 1:00 pm

Mumps Virus Glycan Receptors: Sickening Sweet, but Low-Carb?
Donald R. Latner, PhD
Center for Disease Control and Prevention, Atlanta, GA

Since 2006, there have been several relatively large outbreaks of mumps virus among highly vaccinated populations in the U.S. The basis for these outbreaks is not clear since there is only one serotype of virus and since there are no parameters of the immune response that are known to reliably assure protection from symptomatic disease. In certain individuals, wildtype mumps virus infection generates poorly protective immunity as evidenced by recurrent symptomatic infections. Similarly, certain individuals who have received two or even three doses of vaccine are susceptible to symptomatic infection. (parotitis, and orchitis in post-pubertal males). In contrast, it is estimated that as many as 30% of immunologically naïve individuals experience no symptoms following wildtype infection, despite evidence of seroconversion. The reasons for this divergence in clinical outcomes are unknown.

Mumps virus requires sialic acid to bind and enter the host cell, and previous reports suggest that mumps binds sialic acid in 2,3, 2,6, and 2,8 linkages, with a neurovirulent strain showing preference for 2,6 binding. A very recent report by Kubota et al (2016 PNAS,113:11579-11584; PMID 27671656) indicates that several mumps strains bind only 2,3 sialic acid in simple unbranched trisaccharides and that binding is inhibited by branched glycan structures. While these studies have used a limited number of glycans, we propose to utilize an extensive library of glycan structures available through the Emory Glycomics Core Facility to more fully characterize mumps receptor binding. We hypothesize that variation in host expression of specific glycan structures may contribute to individual susceptibility to symptomatic infection and to the characteristic pathology.

Latner DR and Hickman CJ (2015) “Remembering Mumps” PLoS Pathog. 2015 May 7;11(5):e1004791.



September 15, 2016

Glycomics Data Club

September 27, 2016
12:00 – 1:00 pm

The Oligosaccharides of Human Milk: A Human Metaglycome Its Structure and Function
David F. Smith, PhD
Director ECGC
Department of Biochemistry Emory University School of Medicine

Human milk contains a rich set of soluble, reducing glycans whose functions and bioactivities are not well understood. Because human milk glycans (HMGs) have been implicated as receptors for various pathogens, we explored the functional glycome of human milk using shotgun glycomics. The free glycans from pooled milk samples of donors with mixed Lewis and Secretor phenotypes were labeled with a fluorescent tag and separated via multidimensional HPLC to generate a tagged glycan library containing 247 HMG targets that were printed to generate the HMG shotgun glycan microarray (SGM). We interrogated the HMG SGM with recombinant forms of VP8* domains of the rotavirus (RV) outer capsid spike protein VP4 from human neonatal strains and a bovine strain. Glycans bound by RV attachment proteins were selected for detailed structural analyses using metadata assisted glycan sequencing, which compiles data on each glycan based on its binding by antibodies and lectins before and after exo- and endo-glycosidase digestion of the SGM, coupled with independent MSn analyses. These complementary structural approaches resulted in the identification of 32 glycans based on RV VP8* binding, many of which are novel HMGs. Although sialic acid has been thought to be important as a surface receptor for RVs, our studies indicated that sialic acid is not required for binding of glycans to individual VP8* domains, and each VP8* recognized specific glycan determinants within a unique subset of related glycan structures where specificity differences arise from subtle differences in glycan structures.

Molecular & Cell Proteomics, 13(11): 2944-60. PMID: 25048706.



June 1, 2016

ECGC Acquires New Glycan Microarray

We have recently acquired a glycan microarray that presents the glycan determinants representing the human blood group structures; Blood Group A, Blood Group B, and Blood Group O (H) on 6 different core structures.  The structures designated H, B, and A types I through VI are shown in the table below:

Human Blood Group Array

The description of the synthesis of these glycans is found in the following references:

  • Meloncelli, P.J., and Lowary, T.L. 2010. Synthesis of ABO histo-blood group type I and II antigens. Carbohydrate research 345:2305-2322.
  • Meloncelli, P.J., West, L.J., and Lowary, T.L. 2011. Synthesis and NMR studies on the ABO histo-blood group antigens: synthesis of type III and IV structures and NMR characterization of type I-VI antigens. Carbohydrate research 346:1406-1426.
  • Meloncelli, P.J., and Lowary, T.L. 2009. Synthesis of ABO Histo-Blood Group Type V and VI Antigens. Australian Journal of Chemistry 62:558-574.

The production of the ABH glycan microarray and an application are described in the following reference:

  • Jeyakanthan M, Meloncelli PJ, Zou L, Lowary TL, et al…. ABH-Glycan Microarray Characterizes ABO Subtype Antibodies: Fine Specificity of Immune Tolerance After ABO-Incompatible Transplantation. Am J Transplant 2016; 16: 1548–1558.